Metal-catalyzed, cross-coupling reactions have, in general, become an important synthetic tool for the construction of carbon-carbon bonds (Scheme 1) (1, 2). 
This fundamental transformation has been demonstrated to occur with a variety of organometallic nucleophiles and organic electrophiles typically catalyzed by Ni or Pd. The Suzuki coupling of organoboranes (3) and the Stille (Migita-Kosugi) coupling of organostannanes (4), for example, employ stable, isolable reagents that are extremely weak nucleophiles with good functional group compatibility. Cross-coupling reactions (1, 2) can be used, for example, to construct biaryl subunits which are a commonly found in biologically active molecules (5). Biaryl-containing compounds are also useful in the design of new compounds including organic semiconductors and liquid crystals (6). Existing methods and reagents for metal-catalyzed cross-coupling reactions, however, have some disadvantages, including attenuated and substrate-dependent reactivity, oxygen-sensitivity, high molecule weight and toxicity, which limit their utility and scope of application.
There is continuing interest in the development of new cross-coupling reactions that employ milder procedures and have broader structural generality. Desirable aspects of improved cross-coupling reactions include:(1) increased ease of preparation of the reagents (2) mildness of reaction conditions (3) stereospecificity of reaction (4) functional group compatibility and (5) tractability of by-products.
Hiyama group (7-11, 13) has reported that functionalized organosilanes: aryl and/or alkenylfluorosilanes (7-11), -fluorosiliconates (10a) and -orthosiliconates (10b, 12), do engage in cross-coupling reactions. However, these reagents are difficult to synthesize in geometrically defined form, are difficult to purify and require somewhat harsh reaction conditions for cross-coupling. Silanols (13) have also been demonstrated as appropriate coupling partners. In this reference the authors state “the coupling reaction occurred when Ag2O was employed as an activator,” that “several silver salts resulted in lower yields (AgOTf, 21%); AgBF4, 23%; AgNO3, 16%) and that no reaction occurred under similar conditions when “metal oxides such as CuO, CaO, and BaO” were examined. The authors further state =We currently consider that the role of Ag2O is a base to activate the organosilicon reagent.”
Ideally an organosilicon reagent for use in a cross-coupling reaction will have low molecular weight, be highly effective for cross-coupling, easy to synthesize, stable under chromatographic purification conditions, easily activated toward organic electrophiles, particularly organic halides, and converted to harmless (or at least less toxic) by-products. It is further desirable that the organosilicon reagent be compatible with a variety of functional groups and exhibit stereoselectivity in reaction.
The present invention provides methods for metal-catalized cross-coupling and improved organometallic nucleophiles for use in such reactions.